Improving oxygen delivery during blood transfusions with S-nitrosylation therapy

Phase 1 Study of S-Nitrosylation Therapy to Improve Tissue Oxygenation During Autologous Blood Transfusion in Healthy Volunteer

This study is testing if a special treatment can improve oxygen delivery to tissues during blood transfusions to help people feel better after receiving stored red blood cells.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years to 35 Years
• Sex: All
• Sponsor: Case Western Reserve University (other)
• Locations: 1 site (Cleveland, Ohio)
• Trial ID: NCT03999229 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate whether administering an S-nitrosylating agent can enhance tissue oxygenation during the transfusion of packed red blood cells. The research focuses on the role of S-nitrosothiols in regulating blood flow and oxygen delivery, particularly in the context of stored red blood cells, which often fail to improve oxygenation in recipients. By investigating the effects of SNO therapy alongside RBC transfusion, the study seeks to address the limitations of current transfusion practices and potentially restore the physiological activity of banked blood.

Who should consider this trial

Good fit: Ideal candidates for this study are healthy, non-pregnant adults with hemoglobin levels greater than 12 g/dl and no pre-existing blood disorders.

Not a fit: Patients with pre-existing medical conditions affecting oxygen delivery or those who are pregnant or breastfeeding may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve oxygen delivery in patients receiving blood transfusions, enhancing their recovery and overall health outcomes.

How similar studies have performed: While the approach of using S-nitrosylation in transfusion settings is novel, previous studies have indicated potential benefits of enhancing blood flow and oxygen delivery through similar mechanisms.

Eligibility criteria

Eligibility Criteria

Recruiting and studying of healthy human subjects with no pre-existing pathologic conditions from the local population. As a result the inclusion criteria is deliberately broad.

Inclusion Criteria

1. Hemoglobin \> 12 g/dl
2. Healthy, non-pregnant adults with no pre-existing blood disorders or disease states that impact oxygen delivery.

2a. Active blood and platelet donors will be sought as study participants since these individuals are familiar with the routines for blood withdrawal and re-infusion.

Exclusion Criteria

The exclusion criteria is derived from the American Red Cross(ARC) Standard Operating Procedure (SOP) for autologous donation AND the parameters set out in the investigational new drug application (IND).

1. Individuals who are pregnant, breastfeeding, or are unwilling to avoid pregnancy during the study.
2. Individuals with an anatomic anomaly that would increase the risks associated with placement of the vascular catheters.
3. Individuals who report chronic diseases requiring medication of the heart, lungs, kidney, liver, etc or afflicted with any acute or chronic pathology that in the opinion of the screening physician makes them unsuitable for study.
4. Individuals with a recent history of antibiotic therapy (check for underlying cause).
5. Individuals unwilling to refrain from taking any phosphodiesterase 5 (PDE-5) inhibitor for at least 24 h prior to donation and/or autologous transfusion.
6. Individuals taking a vitamin K antagonist (warfarin) or other anticoagulant (e.g. heparin, clopidogrel, enoxaparin or dalteparin).
7. Individuals taking allopurinol, beta-adrenergic blockers, tricyclic antidepressants, meperidine (or related central nervous system (CNS) agents), or nitrates.
8. Individuals on long-term antihistamine therapy 8a. The study physician will determine on a case by case basis the suitability for inclusion of individuals who control seasonal or acute allergies with occasional antihistamine use.
9. Individuals with blood pressure parameters outside the normal range, i.e., higher than 130 mm Hg systolic and/or higher than 90 mm Hg diastolic; mild hypertension is acceptable by the Red Cross for blood donation.
10. Individuals with heart rates outside the range of 50 to 100 beats per minutes or with a pathologic irregularity.

10a. Pulses lower than 50 may be acceptable if the study participant participates in endurance training. The study physician will be consulted for evaluation.

11\. Individuals with an inherited or acquired blood coagulation disorder, congenital methemoglobinemia, or a familial hemoglobinopathy that impacts oxygen delivery (e.g. sickle cell).

12\. Individuals with any illness that may increase the risks associated with the study.

13\. Individuals who previously received blood products to treat an acute condition will be evaluated on a case by case basis.

14\. Individuals who report an acute or chronic disease state that may impact oxygen delivery.

15\. Individuals with evidence of diminished lung capacity.

16\. Individuals who might have difficulty with the placement of a face mask (e.g. claustrophobia, uncontrolled asthma, severe allergies, sensitive skin) and/or the inhalation of a product for approximately 2-3 hours.

Where this trial is running

Cleveland, Ohio

• University Hospitals Cleveland Medical Center — Cleveland, Ohio, United States (RECRUITING)

Study contacts

• Principal investigator: James D. Reynolds, PhD — Case Western Reserve University
• Study coordinator: James D Reynolds, PhD

Conditions: Transfusion Related Complication, S-Nitrosylation, Tissue Oxygenation, Anemia-induced tissue hypoxia, Red blood cell Transfusion